Carbenoxolone (CBX) has a neuroprotective effect in experimental models of brain ischemia and trauma. However, systemic effect of CBX on ischemic reperfusion injuries has not been investigated in a temporary model of focal cerebral ischemia. Male Wistar rats (n = 32) were divided into control and CBX-treated (100, 200, or 400 mg/kg, intraperitoneally) groups. Transient focal cerebral ischemia was induced by 60-minute middle cerebral artery occlusion by filament method, followed by 23-hour reperfusion. At the end of 24-hour ischemia, neurologic deficit score was tested and infarct volumes were determined using triphenyltetrazolium chloride staining. Administration of CBX (100, 200, or 400 mg/kg) at the beginning of ischemia significantly reduced cortical infarct volumes by 48%, 58%, and 63%, and striatal infarct volumes by 34%, 63%, and 63%, respectively. Nevertheless, CBX has no effect on neurologic dysfunction. Our findings indicated that peripheral administration of CBX has a neuroprotective effect on postischemic damage in a temporary model of focal cerebral ischemia in rat.